激活过氧化物酶增殖物激活受体对血管紧张素Ⅱ诱导内皮细胞中单核细胞趋化因子-1表达的影响

Effects of PPARs agonists on the MCP-1 expression induced by Ang Ⅱ in endothelial cells

目的探讨血管紧张素Ⅱ(AngⅡ)对人脐静脉内皮细胞分泌单核细胞趋化因子-1 (MCP-1)的影响,以及激活过氧化物酶增殖物激活受体(PPARs)中α、γ亚型对MCP-1的影响。方法以RT-PCR和ELISA方法测定AngⅡ在不同浓度(10-8-10-6 mol/L)对人脐静脉内皮分泌MCP-1的影响以及血管紧张素Ⅱ1型受体(AT1R)拮抗剂缬沙坦的干预作用;同时分析PPARα配体非诺贝特及PPARγ配体罗格列酮的干预对AngⅡ诱导MCP-1表达的效应。结果AngⅡ显著刺激人脐静脉内皮细胞系(HUVEC-12)表达MCP-1,增加的程度与AngⅡ的浓度呈正相关,罗格列酮和非诺贝特均可呈浓度依赖的抑制HUVEC-12中由AngⅡ所诱导的MCP-1的表达。结论AngⅡ可刺激HUVEC-12细胞表达MCP-1,其作用与AT1R受体相关;激动剂PPARα、PPARγ均可明显抑制AngⅡ所诱导的内皮细胞中MCP-1表达。

Objective To study the effect of angiotensin Ⅱ on the expression of monocyte chemoattractant protein-l（MCP-1） in cultured human umbilical vein endothelial cells（hUVEC）, and the effect of peroxisome proliferator- activated receptors （PPARs） α and γ on MCP-1. Methods MCP-1 protein level was detected by enzyme-linked immunosorbent assay （ELISA） method, and the mRNA expression level of MCP-1 was determined by RT-PCR. Results Angiotensin Ⅱ distinctly increased the expression of MCP-1 in a dose-dependent manner in cultured hUVECs, and valsartan inhibited the expression of MCP-1 remarkably. Both rosiglitazone （PPARy agonist） and fenofibrate （PPARa agonist） concentrationdependently reduced the expression of MCP-1 in induced by Ang Ⅱ 10^-6 mol/L. Conclusions Angiotensin Ⅱ can increase the expression of MCP-1 evidently in hUVECs, which is inhibited by valsartan. The activation of PPARα and PPARγ can decrease the expression of MCP-1 in hUVECs.